Thrombotic Thrombocytopenic Purpura-Then and Now

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a potentially life-threatening disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and formation of microthrombi in several organs. The disease may manifest once in a lifetime or may relapse after complete recovery of the initial episode; in these recurrent cases, death or neurological sequelae are common final outcomes. Accumulation of unusually large (UL) von Willebrand factor (VWF) multimers was described in the plasma of patients with TTP. Such ULVWF multimers are synthesized in endothelial cells and megakaryocytes and are secreted into the blood upon stimulation. However, in healthy individuals ULVWF multimers do not normally circulate because they are rapidly reduced into smaller multimers soon after their secretion due to cleavage by a plasma metalloprotease, ADAMTS13. Deficiency of ADAMTS13 has been reported consistently in patients with TTP. Such defect may be constitutive, due to homozygous or double heterozygous mutations in the corresponding gene, or acquired, due to the presence of circulating inhibitory antibodies. It follows that in TTP patients, the absent or severely depressed plasma ADAMTS13 activity limits the cleavage of ULVWF multimers, which remain anchored to the endothelial cells in long strings. Particularly under conditions of high shear stress, the multimers may promote the adhesion of circulating platelets, initiating thrombus formation. The clinical implications of these findings to the diagnosis and treatment of TTP are discussed.

Thrombotic thrombocytopenic purpura with concomitant small- and large-vessel thrombosis, atypical posterior reversible encephalopathy syndrome and cerebral microbleeds

“…Early recognition and prompt use of plasma exchange in TTP provide the best chance of recovery for patients. ADAMTS13 plasma level and its antibodies could be used as a diagnostic test for TTP [ 11 ]. However, as the assay may not be widely available, a high index of clinical suspicion would be important to establish a timely diagnosis.…”

Case report of a patient with Klinefelter syndrome treated with testosterone injections presenting with thrombotic thrombocytopenic purpura

“…TTP, first described in 1925, is reported to have an annual incidence of 4 to 11 cases per million people with a mortality of 90% if left untreated [1,2] . The syndrome, initially classified as a pentad of thrombocytopenia, MAHA, fluctuating neurologic signs, renal impairment and fever was later revised to include anyone with thrombocytopenia and MAHA [3] . Pathogenesis includes a deficiency of ADAMTS13, a von Willebrand Factor (vWF) cleaving metalloprotease protein [4,5] .…”

A young woman with fever and loss of consciousness

“…Thrombotic microangiopathy (TMA) is indicated by thrombocytopenia in the full blood count and microangiopathic haemolytic anaemia on the blood film 1. ADAMTS13 enzyme activity <5% is pathognomonic for TTP, and coagulation and haemolysis are typically normal in TTP 12…”

“…ADAMTS13 enzyme activity <5% is pathognomonic for TTP, and coagulation and haemolysis are typically normal in TTP 12…”